von Creytz Isabel, Gerresheim Gesche K, Lier Clemens, Schneider Jana, Schauflinger Martin, Benz Marcel, Kämper Lennart, Rohde Cornelius, Eickmann Markus, Biedenkopf Nadine
Institute of Virology, Philipps-University Marburg, 35043 Marburg, Germany.
German Center for Infection Research (DZIF), Partner Site Giessen-Marburg-Langen, 35043 Marburg, Germany.
Heliyon. 2023 Aug 29;9(9):e19613. doi: 10.1016/j.heliyon.2023.e19613. eCollection 2023 Sep.
Marburg virus (MARV) is a causative agent of a severe hemorrhagic fever with high fatality rates endemic in central Africa. Current outbreaks of MARV in Equatorial Guinea and Tanzania underline the relevance of MARV as a public health emergency pathogen. In 2021, the first known human MARV case was confirmed in Guinea, West Africa. Since no infectious virus could be isolated from that fatal case in 2021, we generated recombinant (rec) MARV Guinea by reverse genetics in order to study and characterize this new MARV, which occurred in West Africa for the first time, in terms of its growth properties, detection by antibodies, and therapeutic potential compared to known MARV strains. Our results showed a solid viral replication of recMARV Guinea in human, bat, and monkey cell lines in comparison to other known MARV strains. We further demonstrated that replication of recMARV Guinea in cells can be inhibited by the nucleoside analogue remdesivir. Taken together, we could successfully reconstitute the first West African MARV from Guinea showing similar replication kinetics in cells compared to other central African MARV strains. Our reverse genetics approach has proven successful in characterizing emerging viruses, especially when virus isolates are missing and viral genome sequences are incomplete.
马尔堡病毒(MARV)是一种在中非流行的、导致高死亡率严重出血热的病原体。当前在赤道几内亚和坦桑尼亚爆发的马尔堡病毒疫情凸显了其作为公共卫生紧急病原体的重要性。2021年,西非几内亚确认了首例已知的人类马尔堡病毒病例。由于无法从2021年的那例致命病例中分离出具有传染性的病毒,我们通过反向遗传学技术构建了重组(rec)马尔堡病毒几内亚株,以便从其生长特性、抗体检测以及与已知马尔堡病毒株相比的治疗潜力等方面,对首次出现在西非的这种新型马尔堡病毒进行研究和表征。我们的结果表明,与其他已知的马尔堡病毒株相比,recMARV几内亚株在人、蝙蝠和猴细胞系中具有稳定的病毒复制能力。我们进一步证明,核苷类似物瑞德西韦可以抑制recMARV几内亚株在细胞中的复制。综上所述,我们成功地从几内亚构建了第一株西非马尔堡病毒,其在细胞中的复制动力学与其他中非马尔堡病毒株相似。我们的反向遗传学方法已被证明在表征新兴病毒方面是成功的,特别是在缺少病毒分离株且病毒基因组序列不完整的情况下。
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